Recent studies in women and nonhuman primates suggest that vascular endothelial growth factor (VEGF) produced by luteinizing granulosa cells plays a physiologic role in the neovascularization of the developing corpus luteum and a pathologic role in ovarian hyperstimulation syndrome. The objectives of this project were (1) to define relationships between serum and follicular fluid (FF) levels of VEGF, estradiol (E2) and progesterone (P4) in IVF patients at the time of egg retrieval; (2) to examine serum VEGF concentrations during early gestation in order to quantify the in vivo effects of hCG on VEGF production; and (3) to report serial measurements of serum and ascites fluid VEGF levels in a patient with severe ovarian hyperstimulation syndrome (OHSS). Serum, FF and/or peritoneal fluid samples were collected from patients undergoing in vitro fertilization (IVF) protocols and/or embryo transfer (ET), including one patient who was hospitalized with severe OHSS. Samples were assayed for estradiol (E), P4 and VEGF content. Data were analyzed by one way ANOVA and unpaired t-tests. At the time of egg retrieval, FF VEGF concentrations were positively correlated (p<0.05) with serum and FF P4 concentrations, and patients' age. By 11-14 days following ET, pregnant recipients of autologous fresh embryos had higher (p<0.05) serum VEGF levels than non-pregnant recipients. Likewise, these recipients had higher serum VEGF levels than pregnant recipients of donor eggs who underwent pituitary down-regulation and steroid hormone replacement. In both IVF and spontaneous pregnancies, serum VEGF levels subsequently declined as the hCG levels increased and gestation progressed. Elevated serum levels of VEGF in a patient with severe OHSS coincided with the clinical onset and recurrence of symptoms. Thus, FF VEGF levels around the time of ovulation correlate with the degree of follicular luteinization. Elevated serum VEGF levels coincide with the onset of endogenous hCG production in pregnant recipients of autologous fresh embryo transfer but not in recipients of donor eggs. Therefore, there is a significant ovarian contribution to circulating VEGF levels during early gestation which declines as pregnancy progresses. Further elevation of serum VEGF levels may contribute to the clinical onset of OHSS symptoms.